Ocular Herpes Simplex Virus-1 (HSV-1) infection is a major cause of corneal scarring and blindness, mostly as a result of HSV-1 recurrences following establishment of latency. In rabbits and mice less than 10% of the HSV-1 genome is expressed during latency. Only one or two discrete HSV-1 genomic regions appear to be involved (Rock, Nesburn and Wechsler 1987). The RNA(s) and their potential proteins may play significant roles in initiation and/or maintenance of ocular (trigeminal ganglionic) HSV-1 latency. We have found similar transcriptionally active regions in latently infected human trigeminal ganglionic neurons (unpublished). In the rabbit ocular model of HSV-1 latency, reactivation and clinical recurrence can be readily induced. We will use this ocular model to study the HSV genes and gene products that are involved in establishment, maintenance, and reactivation of latent HSV-1 infection. We will map the genes expressed during latency and characterize the latency related RNAs (LR-RNAs) and their proteins. In vivo reactivation will be studied to determine what is occurring during the early hours of reactivation under "normal" in vivo conditions, in an animal that suffers natural recurrences of HSV-1 ocular shedding. The ease of establishing latency and inducing reactivation in the ocular rabbit model will also allow us to analyze HSV-1 deletion mutants for latency and reactivation competency. Our long term goal is to use this information to develop efficacious modes of intervention in ocular HSV-1 infection, thereby alleviating a major cause of viral induced blindness. A detailed molecular understanding of ocular viral latency and reactivation should help lead to the development of methods for preventing the establishment and reactivation of HSV-1 latency in the ocular and nonocular setting. This also will be important in the development of an HSV-1 vaccine that does not itself establish latency.